This application is a request for funds to purchase a Nikon A1R HD25 confocal microscope. This microscope will be housed in the Structural and Functional Imaging Core at the Winifred Masterson Burke Medical Research Institute (DBA Burke Neurological Institute; BNI). The Burke Neurological Institute is a leading nonprofit scientific research institute with the mission to find cures for chronic neurological disabilities. The mandate of the imaging core facility is to provide access to a range of light microscopy systems and provide technical assistance with image acquisition, processing, and analysis to all research groups within BNI. Confocal microscopy is essential for the majority of the NIH-funded laboratories at BNI and the previous shared confocal, a Zeiss LSM 510, has exceeded its serviceable lifetime. The Nikon A1R HD25 is both a significant upgrade and a much-needed resource for the NIH-funded laboratories of BNI. The A1R HD25 has many advanced features that would benefit our research progress; however, there are three key features that make it most suitable for the diverse studies that are performed in the Imaging Core: 1) the largest available working field of 25 mm, 2) the industry-leading environmental chamber with multi-dish holder, temperature controller and built-in digital gas mixer, and 3) Nikon's versatile Perfect Focus System (PFS), which corrects for focus drift caused by temperature changes or mechanical disturbances. The institute is highly supportive of this application and has pledged to invest in the maintenance and operation throughout its useful lifetime, as it has done for 17 years on our previous multi-user confocal microscope. The requested microscope will exert a sustained, powerful influence on the conduct of the current NIH-funded research programs at BNI, and will be critical to the success of new studies as they mature to NIH funding.